Biopsy-verified vulvar lichen sclerosus: Incidence trends 1997-2022 and increased risk of vulvar squamous precancer and squamous cell carcinoma.

Population-based data on the epidemiology of vulvar lichen sclerosus (LS) are sparse and only few prospective studies have investigated the malignant potential of the disease. We used the nationwide Danish Pathology Registry to first assess the incidence of biopsy-verified vulvar LS in the period 1997-2022 and second to examine the incidence of vulvar high-grade squamous precancer and squamous cell carcinoma (SCC) in women with biopsy-verified vulvar LS (1978-2019) compared with that expected in the general female population. For the latter aim, we computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). During our study period, the age-standardized incidence rate of vulvar LS increased from 5.0 (1997-1998) to 35.7 (2021-2022) per 100,000 person-years. Compared with the general female population, women with biopsy-verified vulvar LS had significantly increased rates of vulvar high-grade squamous precancer (SIR = 8.5; 95% CI: 7.2-10.0) and SCC (SIR = 16.2; 95% CI: 14.2-18.4). The SIRs of vulvar high-grade squamous precancer and SCC did not vary substantially according to length of follow-up. This nationwide and population-based study shows a 7-fold increase in the incidence of biopsy-verified vulvar LS since 1997. Data also show that women with biopsy-verified vulvar LS have 8.5 and 16 times higher than expected incidence of vulvar high-grade squamous precancer and SCC, respectively. The substantially increased incidence of vulvar high-grade squamous precancer and SCC following LS is important in relation to the clinical management and follow-up of LS patients.

DNA Methylation and p53 Immunohistochemistry as Prognostic Biomarkers for Vulvar Lichen Sclerosus.

Vulvar lichen sclerosus (LS) is an inflammatory dermatosis that can progress to human papillomavirus (HPV)-independent vulvar intraepithelial neoplasia (HPVi VIN) and vulvar squamous cell carcinoma (VSCC). Although LS has a much lower cancer risk compared with HPVi VIN (5% vs 50%, respectively), its incidence is significantly higher. Therefore, there is a clinical need to identify LS patients with an increased cancer risk. Our objective was to study the value of DNA methylation and p53 immunohistochemistry (IHC) as prognostic biomarkers for progression to cancer in patients with LS. Vulvar tissues from 236 patients were selected, including 75 LS and 68 HPVi VIN, both with and without cancer development, 32 VSCC, and 61 healthy vulvar controls. Samples were subjected to p53 IHC and DNA methylation analysis of a 3-gene marker panel containing ZNF582, SST, and miR124-2. Methylation levels and p53 IHC status (mutant or wild-type) were assessed and compared among all disease categories. Odds ratios were determined to identify whether the biomarkers were associated with progression to cancer in patients with LS. The highest methylation levels were found in HPVi VIN and VSCC, followed by LS and healthy vulvar controls. The largest heterogeneity in methylation levels was observed in LS cases. In fact, the 3-marker panel tested positive in 70% of LS, which progressed to VSCC vs only 17% of LS in patients without cancer development (P = .002). Also, mutant p53 IHC was observed more frequently in LS with progression to VSCC compared with nonprogressive LS cases (42% vs 3%, respectively, P = .001). Multivariable analysis identified a mutant p53 status as the only independent risk factor for cancer development in LS (odds ratio: 34.0, 95% CI: 1.4-807.4). In conclusion, DNA methylation testing and p53 IHC show strong potential as prognostic biomarkers for the identification of LS patients at high risk of progression to cancer.

Advances in the pathogenesis of vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic non-neoplastic skin lesion characterized by vulvar itching, pain, atrophy, whitening of the skin and mucous membranes, and gradual atrophy and disappearance of the labia minora, which can eventually lead to vulvar scarring, causing functional impairment and seriously affecting the patient's physical and mental health. VLS can occur at any age, however, its pathogenesis and etiology are not fully understood. Considerable progress has been made in related research on genetic susceptibility factors, autoimmune disorders, collagen metabolism abnormalities, and their triggering factors in disease formation and progression. This article reviews the etiology of vulvar lichen sclerosus.

A Preliminary Study Using High-Frequency Ultrasound to Evaluate Vulvar Skin With Lichenoid Vulvar Dermatoses.

BACKGROUND: Lichenoid vulvar dermatoses (LVD) are inflammatory diseases primarily affecting the vulva and anus. This study aims to evaluate the skin changes in patients with LVD using high-frequency ultrasound. METHODS: Forty-five patients with LVD, who attended Henan Provincial People's Hospital from November 2021 to March 2024, were selected. According to the pathological conclusions, patients were divided into two groups: the vulvar lichen sclerosus (VLS) group (n = 24) and the vulvar lichen simplex chronicus (VLSC) group (n = 21). Thirty age- and BMI-matched healthy women were selected as the control group. We assessed the epidermal thickness, subepidermal low echogenic band (SLEB) thickness, dermal thickness, and vascular index (VI) among the three groups. Receiver operating characteristic curve (ROC) analysis was performed to determine the diagnostic efficacy of these ultrasound parameters for LVD. Binary logistic regression was used to investigate risk factors influencing LVD pathology in VLS patients. RESULTS: Epidermal thickness, SLEB thickness, dermal thickness, and VI were increased in the VLS and VLSC groups compared to the control group (p < 0.05). There were no statistically significant differences in ultrasound parameters between the VLS and VLSC groups (p > 0.05). The ROC curves showed that the area under the curve (AUC) value for the dermis (AUC = 0.882) was the largest for VLS, and VI (AUC = 0.917), it was the largest for VLSC. Binary logistic regression indicated that having an allergic disease was a risk factor for VLS between VLS and VLSC groups (OR = 6.797, p = 0.028). CONCLUSION: High-frequency ultrasound can detect thickening of the skin and increasing VI in patients with LVD, which can be helpful in the evaluation and management of LVD.

A Mimicker of Differentiated Vulvar Intraepithelial Neoplasia: Reactive Atypia From Noncompliance With Lichen Sclerosus Therapy.

ABSTRACT: Differentiated vulvar intraepithelial neoplasia (d-VIN) is an HPV-independent precursor to vulvar squamous cell carcinoma. The histology of d-VIN lesions is difficult to differentiate from that of non-neoplastic epithelial disorders, especially lichen sclerosus (LS). The authors present a case of LS, where relying on histopathology alone could have led to misdiagnosis. The patient was a 17-year-old female patient with clinical features of vulvar dermatitis and LS for 2 years. She was counseled to apply clobetasol 0.05% to the affected area daily but reported no improvement after 6 months. A biopsy of the right labia majora revealed histologic findings typical of d-VIN and near-contiguous p53 expression. These features are characteristic of d-VIN. However, d-VIN is exceedingly rare in young patients. The case was reviewed by 6 dermatopathologists and gynecologic pathologists, who observed that the degree of inflammation would be unusual postclobetasol therapy and could be due to noncompliance. A review of the patient's chart revealed that she "does not always remember to apply" clobetasol. The patient's clinician confirmed that there were compliance issues, and the follow-up biopsy was negative for d-VIN. The case was signed out as LS, with a note describing the above, and to rebiopsy if concern persisted. The authors conjecture that inflammatory infiltrates in the biopsied area caused reactive atypia due to lack of adherence to treatment. Although the patient's age helped rule out d-VIN, similar cases in elderly patients may be occurring. Pathologists must be aware that reactive forms of untreated LS can mimic d-VIN, to avoid misdiagnosis.

Vulvar Lichenoid Dermatoses With Emphasis on the Distinction Between Lichen Sclerosus and Lichen Planus: A 10-Year Study.

OBJECTIVES: Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted. METHODS: Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done. RESULTS: There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%). CONCLUSION: Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.

Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologic oncologists in The Netherlands.

BACKGROUND: Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). METHODS: An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. RESULTS: Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. CONCLUSION: The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.

Vulvar lichen sclerosus (LS) is a chronic skin condition which may progress to vulvar squamous cell carcinoma (VSCC) through differentiated vulvar intraepithelial neoplasia (dVIN). LS symptoms are treated with topical corticosteroids (TCS), which can also prevent progression to dVIN and VSCC. However, current international guidelines do not give any recommendation on the treatment of LS following surgery for VSCC. To evaluate the current management of LS patients without a history of VSCC (LS^noVSCC) and patients with LS following surgery for VSCC (LS^VSCC), a survey study was conducted among all gynaecologic oncologists (GOs) in The Netherlands. The findings of this study demonstrate that Dutch GOs prescribed TCS more often to patients with LS^noVSCC as compared to patients with LS^VSCC. However, when deciding to prescribe TCS, the majority of Dutch GOs prescribed ultra-potent TCS for an indefinite period of time for both LS^noVSCC and LS^VSCC patients.

[Clinical and pathological analysis of 345 cases of vulvar lichen sclerosus and a preliminary study on the frequency of maintenance treatment].

Objective: To analyze and summarize the clinical and pathological characteristics, management, and efficacy of patients with vulvar lichen sclerosus (VLS) through a single center large sample study, and preliminarily to explore the frequency of maintenance treatment medication for VLS. Methods: The clinical data of VLS patients in Obstetrics and Gynecology Hospital of Fudan University from 2018 to 2021 were retrospectively collected. The clinicopathological characteristics (patients' age, course of disease, complicated disease history, family history, symptoms, signs and pathology), treatment and effects were retrospectively analyzed. The patients in the maintenance treatment stage were followed up regularly to explore the minimum frequency of individual medication to maintain the stability of the disease. Results: (1) General situation: a total of 345 patients with VLS were included in this study. The average age was (50.4±14.7) years (ranged from 8 to 84 years old), prevalence was highest in the 50-59 years group (30.1%, 104/345). Immune diseases occurred in 18.6% (33/177) of patients, 24.3% (43/177) of patients had allergic skin diseases, and 5.6% (10/177) of the patients' immediate family members had chronic vulvar pruritus or vulvar hypopigmentation. (2) Clinical features: the most common symptom was vulvar pruritus (96.1%, 196/204) among 204 patients with recorded symptoms. The most common sign was hypopigmentation of the vulva (96.3%, 206/214). The most common involved sites were labia minora (70.3%, 142/202), labia majora (67.8%, 137/202), and labial sulcus (59.4%, 120/202). The cumulative number of sites involved in 62 vulvar atrophy patients (2.7±1.1) was significantly higher than that in 152 non-atrophy patients (2.2±1.0; t=3.48, P=0.001). The course of vulvar atrophy was (9.3±8.5) years, which was significantly longer than that of non-atrophy patients [(6.6±5.6) years; t=2.04, P=0.046]. (3) Pathological features: among the 286 patients with electronic pathological sections, the most common pathological feature in the epidermis was epithelial nail process passivation (71.3%, 204/286). The common pathological features in the dermis were interstitial collagenization (84.6%, 242/286), and inflammatory cell infiltration (73.8%, 211/286). (4) Treatment: 177 patients received standardized treatment after diagnosis and were followed up regularly in our hospital. In the initial treatment stage, 26.0% (46/177) of the patients were treated with 0.05% clobetasol propionate cream, and 74.0% (131/177) of the patients were treated with 0.1% mometasone furoate ointment. The complete remission rates of the two methods were respectively 80.4% (37/46) and 74.0% (97/131), and there was no statistically significant difference (χ²=0.76, P=0.385). During maintenance treatment, 27.1% (48/177) of the patients took the medication twice a week, 35.0% (62/177) took the medication once a week, and 37.9% (67/177) took the medication once every 10 days. During follow-up after 6 months of maintenance treatment, there were no patients with recurrence of pruritus or progression of vulvar signs. Conclusions: The majority of VLS patients have itching, hypopigmentation, involvement of labia minora and labia majora, progressive atrophy, and inflammatory infiltration of dermis. Local treatments of mometasone furoate and clobetasol propionate have good initial therapeutic effects. The frequency exploration of individualized maintenance treatment could minimize the occurrence of adverse reactions when ensuring the stability of the patients' condition.

Differential proteomic expression profiles in vulvar lichen planus as compared to normal vulvar tissue, vulvar lichen sclerosus, or oral lichen planus: An exploratory study.

Vulvar lichen planus (VLP) is a chronic inflammatory disease which adversely affects patients' quality of life. The pathogenesis of VLP is unknown although Th1 immune response has been implicated. We aimed to discover specific tissue-based protein biomarkers in VLP compared to normal vulvar tissue (NVT), vulvar lichen sclerosus (VLS) and oral lichen planus (OLP). We used laser capture microdissection-liquid chromatography- tandem mass spectrometry to assess protein expression in fixed lesional mucosal specimens from patients with VLP (n = 5). We then compared proteomic profiles against those of NVT (n = 4), VLS (n = 5), OLP (n = 6) and normal oral mucosa (n = 5), previously published by our group. IL16, PTPRC, PTPRCAP, TAP1 and ITGB2 and were significantly overexpressed in VLP compared to NVT. Ingenuity pathway analysis identified antigen presentation and integrin signalling pathways. Proteins overexpressed in both VLP versus NVT and OLP versus NOM included IL16, PTPRC, PTPRCAP, TAP1, HLA-DPB1, HLA-B and HLA-DRA. This proteomic analysis revealed several overexpressed proteins in VLP that relate to Th1 autoimmunity, including IL16. Overlapping pathways, including those involving IFNγ and Th1 signalling, were observed between VLP, VLS, and OLP.

Long-term consequences of juvenile vulvar lichen sclerosus: A cohort study of adults with a histologically confirmed diagnosis in childhood or adolescence.

INTRODUCTION: Vulvar lichen sclerosus (VLS) occurs in at least one in 900 girls. There is limited knowledge as to what extent the disease persists in adulthood and what the repercussions in adulthood may be. The aim of this study is to evaluate the long-term consequences of VLS diagnosed in childhood or adolescence. MATERIAL AND METHODS: The population of females histologically diagnosed with VLS in childhood or adolescence in the Netherlands between 1991 and 2015 was identified through the national pathology database. Histological specimens were retrieved and re-evaluated. Potential participants for whom the diagnosis was reconfirmed and who are now adults, were then traced and surveyed. Descriptive statistics were calculated and compared with the literature. Main outcome measures are the demographics of the cohort, their scores on standardized quality of life (QoL) and sexuality questionnaires and answers to additional questions regarding patients' experience with the disease. The questionnaires used were the Dermatology Life Quality Index (DLQI), the Skindex-29, the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). Secondary outcome measures include obstetric history and histological features found in the original tissue specimens. RESULTS: A total of 81 women participated, median age 29.0 years, median follow-up from childhood diagnosis 19.5 years. Both QoL and sexuality were somewhat affected in 51.9% of cases. Less than half (45%) reported having regular check-ups. Forty-five (56%) reported symptoms within the past year; of those with symptoms, 14 (31%) were not under surveillance. Cesarean section rate (14.5%) was comparable to the general population, and there were more high-grade obstetric anal sphincter injuries with vaginal deliveries than expected. Sixteen respondents (20%) were not aware of the childhood diagnosis prior to this study. CONCLUSIONS: Symptoms due to VLS are reported by most adults diagnosed as juveniles. QoL and sexuality are affected and correlate to recent symptoms. VLS as a juvenile does not preclude a vaginal delivery. Women diagnosed with VLS in childhood or adolescence are often lost to follow-up.

In vivo evaluation of vulvar lichen sclerosus with reflectance confocal microscopy and therapeutic monitoring in children.

BACKGROUND: Vulvar lichen sclerosus (VLS) in girls presents with itching, dysuria, and constipation and may result in the loss of vulvar architecture. In patients with an ambiguous clinical presentation, reflectance confocal microscopy (RCM) could be a helpful noninvasive diagnostic tool. The aim of this study was to describe the RCM characteristics of VLS and explore the clinical application value of RCM in therapeutic monitoring. METHODS: Sixteen patients with VLS were included in the study. All patients were periodically evaluated clinically with RCM, and different treatment regimens were given based on the patient's clinical appearances and RCM features. RESULTS: Some major key diagnostic features of VLS can be observed by RCM, including round to oval cyst-like structures with medium-to-low-refractive keratinoid substances (75%), thinning of the epidermal thickness (100%), destruction of the ring-like structures around dermal papillae (100%), disorderly distributed coarse medium-refractive fibrous material (100%),polygonal, plump, high-refractive cellular structures and linear low-refractive canalicular structures (100%). All of these characteristics had a high correspondence with histopathological features. The clinical manifestations improved after individualized treatment regimens based on the clinical appearances and RCM features. CONCLUSION: RCM allows the visualization of major key diagnostic features of VLS and represents a valid option for objective therapeutic monitoring.

A prospective pilot study to assess for histologic changes on vulvar biopsies in postmenopausal women with lichen sclerosus treated with fractionated CO2 laser therapy.

OBJECTIVES: To investigate the histologic characteristics of vulvar tissues before and after completion of fractionated carbon dioxide (CO2 ) laser therapy (FxCO2) for vulvar lichen sclerosus (LS). The secondary objective was to assess subjective improvement in symptoms via the Skindex-16 questionnaire. METHODS: This prospective single-arm study was conducted from April 2021 to August 2022 at one academic medical center. Ten postmenopausal women with biopsy-proven LS planning FxCO2 laser treatment were enrolled. Exclusion criteria included prior transvaginal mesh for prolapse, topical corticosteroid use within 8 weeks, prior pelvic radiation, malignancy, active genital infection, or pregnancy. The vulvovaginal SmartXide2-V2-LR laser system fractionated CO2 laser (DEKA) was utilized to treat visually affected areas of vulvar and perianal LS with a single pass. Subjects underwent three treatments 4-6 weeks apart. Subjects completed the Skindex-16 questionnaire and had vulvar biopsy at baseline and at 4 weeks after completion of fractionated CO2 laser therapy. Blinded histologic slides were scored by one dermatopathologist (Michael A. Cardis) rating from 1 to 5 the degree of dermal sclerosis, inflammation, and epidermal atrophy. Change scores were calculated as the difference between pre- and post-treatment scores for each subject. RESULTS: The 10 subjects enrolled had a mean age of 61 and most were white, privately insured, and had a college/graduate-level education. Post-fractionated CO2 laser treatment vulvar biopsies showed significant improvement in sclerosis and epidermal atrophy compared with pretreatment baseline biopsy specimens (p < 0.05) with no statistically significant change found in inflammation score. Skindex-16 and FSFI scores showed a trend towards improvement (p > 0.05 for both). A statistically significant correlation was found between change in sclerosis and Skindex-16 symptoms scores with an average change of 21.4 units in Skindex-16 symptoms score for every one-point change in histologic sclerosis score (p = 0.03). CONCLUSIONS: In postmenopausal women with vulvar LS undergoing fractionated CO2 laser, symptomatic improvements correlated with histologic change in degree of sclerosis on vulvar biopsy. These results demonstrate FxCO2 laser therapy as a promising option for the treatment of LS and suggest that further studies should assess degree of sclerosis on histopathology.

Vulvar Lichen Sclerosus Clinical Severity Scales and Histopathologic Correlation: A Case Series.

ABSTRACT: Several vulvar lichen sclerosus (VLS) clinical severity scales have recently been proposed. In this prospective case series, we characterized histopathology in the context of clinical severity in 6 treatment-naïve postmenopausal patients with VLS. The Vulvar Quality of Life Index (VQLI) and an adaptation of the 2018 International Society for the Study of Vulvovaginal Disease Delphi consensus VLS severity score were administered. Vulvar skin punch biopsies were obtained to measure inflammatory density, constituent inflammatory cells, thickness of the stratum corneum and other epidermal layers, dermal edema, and dermal sclerosis. Clinicopathologic correlations were assessed. Two cases demonstrated sparse inflammatory densities, 1 case demonstrated patchy and nodular inflammatory density, 1 case demonstrated dense lichenoid inflammatory density, and 2 cases demonstrated dense lichenoid and epitheliotropic inflammatory densities. Those patients who reported severe pruritus demonstrated the greatest lymphocytic inflammatory densities on histopathological examination. Both cases of ulceration or erosion were associated with severe VQLI scores. Severe VQLI scores were also associated with trends for higher average thickness of the epidermal layers and of dermal sclerosis. Altogether, histopathologic grading of biopsy sites may reflect clinical severity in patients with VLS.

Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis.

PURPOSE: Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. METHODS: This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). RESULTS: In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. CONCLUSIONS: In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

Comorbidity of Urogynecological and Gastrointestinal Disorders in Female Patients With Lichen Sclerosus.

OBJECTIVE: Lichen sclerosus (LS) is a chronic inflammatory disease with a significant impact on quality of life. The aim of this cross-sectional case-control study was to characterize concomitant urogynecological and gastrointestinal disorders in female patients with LS. METHODS: A medical records search between 2004 and 2012 yielded 455 women and girls (mean age 64 years) with LS. The study cohort was compared with a 10-fold age- and sex-matched control cohort. Gynecological cancers and their precursors; gynecological, urinary, and gastrointestinal disorders; and pain syndromes were evaluated. RESULTS: The well-known association between LS and increased risk of vulvar cancer and its precursors was also found in our study (relative risk [RR] = 100.0; p < .001 and high-grade squamous intraepithelial lesions RR = 110.0; p < .001, respectively), but we also found an increased risk for cervical cancer (RR = 6.0; p = .005) and endometrial cancer (RR = 2.9; p < .001). Gynecological pain syndromes such as dyspareunia (RR = 20.0; p < .001) and interstitial cystitis (RR = 5.0; p < .001) and urinary incontinence (RR = 4.8; p < .001) were also increased. Among gastrointestinal disorders, we found increased risk for celiac disease (RR = 6.8; p < .001), diverticular intestine diseases (RR = 1.9; p < .001), functional intestinal disorders (RR = 2.3; p = .003), and anal and rectal fissures (RR = 2.4; p = .046). CONCLUSIONS: We found that female patients with LS have an increased risk for gynecological cancers as well as for several urogynecological and gastrointestinal disorders. Increased awareness is required to identify and treat these concomitant disorders.

[Possibilities of multiphoton microscopy for the diagnosis of the vulvar lichen sclerosus]. / Vozmozhnosti mul'tifotonnoi mikroskopii dlya diagnostiki skleroticheskogo likhena vul'vy.

BACKGROUND: Vulvar lichen sclerosus (VLS) is a chronic and recurrent dermatosis of an inflammatory nature with severe focal atrophy of the skin. Connective tissue changes are polymorphic and are still not taken into account in histological diagnostics due to the difficulty of interpreting routine histological methods. In this work, we use multiphoton microscopy (MPM) as a new imaging technique that provides detailed information about the organization of collagen fibers in the dermis based on a non-linear second harmonic generation (SHG) process. OBJECTIVE: To determine the degree of connective tissue damage in lichen sclerosus using standard histological techniques and to reveal the diagnostic capabilities of multiphoton microscopy. MATERIAL AND METHODS: We studied 42 biopsies with a histopathological diagnosis of VLS and 10 biopsies of normal vulvar skin. Histological, histochemical and immunohistochemical evaluation was used in comparison with MPM data. Quantitative analysis included the determination of the thickness, length of collagen fibers and the average intensity of the SHG signal. RESULTS: A comprehensive study of the skin showed 4 groups of changes that can be regarded as the degree of the dermis damage: initial, mild, moderate, severe. The affected area at the initial and mild degree has subtle changes, however, it is reliably identified by quantitative analysis of the SHG signal. So, the initial degree is characterized by thin (1.3-1.8 µm) long (56-69 µm) collagen fibers, with a moderate degree, the fibers are thickened (3.4-4.3 µm) and fragmented (22-37 µm). The affected area in moderate and severe cases undergoes homogenization, which is associated with the deposition of extremely thin (0.6-0.9 µm) short (16-28 µm) collagen fibers and the expression of type V collagen. CONCLUSION: Multiphoton microscopy in the second harmonic generation mode is a reliable method for identifying collagen fibers in tissues. The study made it possible to identify 4 degrees of the dermis damage in vulvar lichen sclerosus.

Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue.

Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection- and nanoLC-tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow-up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon-γ and antigen-presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy-related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.

Autologous lipoaspirate as a new treatment of vulvar lichen sclerosus: A review on literature.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that mostly affects the genital and anal skin areas. Symptoms may vary from pruritis and pain to sexual dysfunction; however, LS can also be asymptomatic. LS occurs at all ages and in both sexes. Approximately 5% of all women affected by vulvar LS will develop vulvar squamous cell carcinoma. Topical treatment is safe but less effective resulting in chronic course in most patients, who suffer from persistent itching and pain. In severe cases of therapy-resistant LS, there is no adequate treatment. Fat grafting is a novel regenerative therapy to reduce dermal fibrosis. The therapeutic effect of adipose tissue grafts for LS is already investigated in various pioneering studies. This review provides an overview of these studies and the putative mechanisms-of-action of fat grafting to treat LS.

Acquired Elastotic Hemangioma-like Change of the Vulva Associated With Lichen Sclerosus.

Acquired elastotic hemangioma (AEH) is a rare variant of hemangioma that usually presents as an asymptomatic, solitary, slow-growing red plaque on a sun-exposed site of an adult. Ultraviolet radiation can contribute to the pathogenesis of this hemangioma. Lichen sclerosus (LS), a scarring disease, may present a prominent accumulation of elastic fibers in the reticular dermis reflecting a reparative process. Vulvar elastosis, a novel diagnostic entity with fibers similar to solar elastosis, is more common in women 45 yr and older and is related to aging and/or hormonal changes. We herein report for the first time a case of AEH-like change located in the vulva, a sun-protected area, associated with genital LS. An 81-yr-old woman presented with a painful vulvar lesion of 1-yr duration. Clinical examination revealed vulvar LS and 1 cm-flat, erythematous, well-defined plaque with increased consistency located on the left labium minus. Histopathology showed a non-neoplastic proliferation of WT1-positive, small vascular channels surrounded and intertwined by intense elastosis in the reticular dermis. Alpha-smooth muscle actin positive pericytes encircled the vascular channels. The lesion can be understood as a reparative process within an LS with the appearance of epidermal hyperplasia, proliferation of small vascular channels, and hyperplastic elastosis. There is a close link between epidermal hyperplasia and angiogenesis in the formation of this reparative lesion. Recognition of this lesion is crucial to avoid confusion with other significant processes especially Kaposi sarcoma and well-differentiated angiosarcoma.

Acantholytic Squamous Cell Carcinoma Arising From Lichen Sclerosus: A Rare Case Affecting Vulvar Skin.

We present the case of an 82-year-old female with acantholytic squamous cell carcinoma affecting vulvar skin. The patient had a history of perineal lichen sclerosus for 5 years before presentation. She was referred to a dermatologist for intractable severe pain associated with the lesions. Biopsies showed an infiltrative squamous cell carcinoma with histology consistent with the acantholytic subtype. Acantholytic squamous cell carcinoma is a rare histologic variant characterized by dyscohesive keratinocytes with pseudoglandular formation and dyskeratosis. It is associated with sun-damaged skin and most commonly occurs in the head and neck of elderly men. Few cases have been reported at nondermal sites and non-sun-exposed dermis. The patient underwent a radical vulvectomy and bilateral inguinal node dissection. The 1.6 cm tumor was diffusely acantholytic and pseudoglands were present. The tumor cells were diffusely positive for p63 immunohistochemical stain. As expected at this site, there was no solar elastosis identified histologically. However, vulvar intraepithelial neoplasia and chronic lichen sclerosus were apparent. This case represents a rare histologic subtype of squamous cell carcinoma in an unusual site associated with lichen sclerosus instead of solar elastosis.